Project III: Abstract Since their description at the single cell level, mirror neurons (MN) exhibited plasticity, which only in recent years has been considered as a critical feature for understanding their development and their possible contributions to several psychological/behavioral processes. Prior findings in this Program Project demonstrated that the mirror neurons system (MNS) undergoes significant changes depending on social environment and on motor experience. By using different methodologies (single cell recording, EEG and behavioral/ethological assessment) we found that specific social/motor experiences (learning to use a tool, or acting in coordination with social partners) have profound effects on MN activity and on individual?s understanding of others? actions, also when outside their motor repertoire. These findings suggest that: 1) the social environment plays an important role in shaping and refining this system; 2) a larger brain network is likely involved in modulating MN activity and in contributing to social perception; 3) key learning mechanisms are involved in shaping and tuning the MNS. Despite these important achievements, the role of social factors in MNS plasticity and their neurophysiological mechanisms (at the single cell level) have still been largely unexplored and are not well understood. In the current project we propose to address these core questions by investigating in adult macaques A) the activity of MN during learning the use of a tool, b) the neural networks that, together with the parietal-premotor mirror circuit, are involved in action coding during social interactions, and c) the causal role of MN regions to brain EEG signals. Within this context, the primary aims of our research program are as follows: Aim 1. Investigate the effects of visual and sensorimotor experience with tools on monkey premotor MN visual response to tool actions. This study will chronically record for 5 weeks the activity of neurons in the monkey premotor cortex, while she is visually exposed for several weeks to unfamiliar tool actions or trained to use a tool. Aim 2. Determine the role of the social context in modulating activity of neurons in the monkey ventral premotor cortex and ventrolateral prefrontal cortex. We will investigate, in F5 and ventrolateral prefrontal cortex, the activity of MN and other neurons during a visual task requiring a monkey to simply observe an action that, depending on the social context, will be aimed at different goals (social or non-social). Aim 3. Investigate the relation between mu-desynchronization in the alpha and beta frequency band and the activity of MN in the ventral premotor cortex (F5) and the Inferior Parietal Lobule (IPL) of the monkey. Although EEG (mu rhythm) is widely used as an indirect measurement of MN activity, there is yet no direct evidence of this link. To address this issue we will use an innovative method (supported by Core B) of simultaneously recording monkey F5 and IPL MN activity from different cortical layers and EEG activity from the scalp. We will then investigate the causal role of these two regions to the generation of the mu rhythm, by pharmacologically inactivating F5 and IPL, and recording the subsequent alpha and beta EEG modifications.